Abstract: The present invention provides monoclonal antibodies that specifically bind to the extracellular domain of human Claudin-1 on the cell surface, thereby inhibiting HCV entry into susceptible cells and preventing HCV infection of these cells; and hybridoma cell lines which produce such monoclonal antibodies. Also provided are reagents that comprise such antibodies, and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing HCV infection by administration of an inventive monoclonal antibody, or a pharmaceutical composition thereof are also described.